1,2-Dichloroethane → HCID 56654309, 화합물

HRID 242327

반응식

HRID 242327 반응식
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([N:9]2[CH2:24][CH2:23][C:12]3[N:13]=[CH:14][N:15]=[C:16]([O:17][C@H:18]4[CH2:22][CH2:21][NH:20][CH2:19]4)[C:11]=3[CH2:10]2)=[CH:5][C:4]=1[C:25]([F:28])([F:27])[F:26].[CH3:29][N:30]1[CH:34]=[C:33]([C:35](O)=[O:36])[CH:32]=[N:31]1.N1(O)C2C=CC=CC=2N=N1.C(Cl)CCl>C(Cl)Cl>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([N:9]2[CH2:24][CH2:23][C:12]3[N:13]=[CH:14][N:15]=[C:16]([O:17][C@H:18]4[CH2:22][CH2:21][N:20]([C:35]([C:33]5[CH:32]=[N:31][N:30]([CH3:29])[CH:34]=5)=[O:36])[CH2:19]4)[C:11]=3[CH2:10]2)=[CH:5][C:4]=1[C:25]([F:28])([F:26])[F:27]

참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 6431601-Methyl-1H-pyrazole-4-carboxylic acidHCID 57495337HCID 57495337, 화합물2회

생성물 1

HCID 56654309HCID 56654309, 화합물

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a mixture of 6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (prepared using step 1, example 91 from intermediate 13) (44 mg, 0.11 mmol), 1-methyl-1H-pyrazole-4-carboxylic acid (15 mg, 0.12 mmol), benztriazol-1-ol (19 mg, 0.12 mmol) in CH2Cl2 (1.0 mL) was added EDC (34 mg, 0.18 mmol) and the resulting mixture was stirred at rt for 18 h. Partitioned between CH2Cl2 (10 mL) and sat. NaHCO3(aq) (2.0 mL) and the organic layer separated by filtering through a phase separation tube. Concentrated in vacuo and purified by flash chromatography through Biotage® amino silica gel eluting with cyclohexane/EtOAc, 100/0 to 0/100 to give {(S)-3-[6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-pyrrolidin-1-yl}-(1-methyl-1H-pyrazol-4-yl)-methanone as a white lyophilized powder (44 mg, 75% yield). 1H NMR (400 MHz, CDCl3-d, 298K) δ ppm 2.26-2.45 (m, 2H) 3.04-3.10 (m, 2H) 3.49-3.57 (m, 2H) 3.89-4.00 (m, 7H) 4.01 (s, 3H) 4.10-4.18 (m, 2H) 5.78-5.83 (m, 1H) 7.60-7.62 (m, 1H) 7.76-7.89 (m, 2H) 8.04-8.07 (m, 1H) 8.61-8.66 (m, 1H) MS: [M+H]+=504.2, Rt(3)=1.59 min. Example 55 was prepared using procedures analogous to those used in example 54 using appropriate starting materials.

후처리

  1. customPartitioned between CH2Cl2 (10 mL) and sat. NaHCO3(aq) (2.0 mL)
  2. customthe organic layer separated
  3. filtrationby filtering through a phase separation tube
  4. concentrationConcentrated in vacuo
  5. custompurified by flash chromatography through Biotage® amino silica gel eluting with cyclohexane/EtOAc, 100/0 to 0/100

출처 및 근거

ORD 기록
ord-e207732812ac4d5998a15f8facdcc7b1
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653092B2

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